Motivation-opportunity-ability-behaviour of community members and program implementers towards mass drug administration for lymphatic filariasis elimination in India: a systematic review and implementation priority.

Lymphatic filariasis (LF) is a significant public health issue in India. Despite 10-15 rounds of mass drug administration (MDA) in India, the global LF elimination target of 2030 appears challenging. To strengthen the program, community and provider perspectives on ways to bridge a gap in MDA are needed. Through the motivation-opportunity-ability-behaviour (MOAB) lens, we systematically reviewed the facilitators and barriers encountered in LF elimination in India. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched PubMed, Embase, ProQuest and Google Scholar databases to explore factors related to MDA program implementation in India through 30 June 2021. We analysed the data using a thematic framework. We identified 576 studies; of these, 20 studies were included. This review revealed that the public health system for distributing MDA drugs in India created a better enabling environment, including zero out-of-pocket expenditure, door-step distribution of medicines and ample capacity-building training and follow-up. However, community members were unaware of the rationale for drug consumption, leading to a gap in drug distribution and consumption. Motivation is required among community members, which suggests capacity-building training for service providers to counsel the community.

Factors influencing implementation of mass drug administration for lymphatic filariasis elimination: a mixed-method study in Odisha, India.

Background: Lymphatic filariasis (LF) persists as a public health problem in India. Despite more than ten rounds of mass drug administration (MDA), LF continues to be endemic in the Dhenkanal district of Odisha. Hence, we assessed the coverage and compliance of the MDA program and explored the factors affecting it in the Dhenkanal district. Methods: An explanatory mixed-method study was conducted, wherein for the quantitative survey, 552 participants aged 2 years and above were recruited following a multistage cluster random sampling during February 2022. In-depth interviews were conducted among purposively selected key stakeholders and program implementers. Descriptive statistics were used to report coverage and compliance, along with a 95% confidence interval. Qualitative data were analyzed using a thematic approach. Results: We observed coverage of 99.28% and compliance of 85.87% for MDA drugs. Supervised drug administration proved to be a major pillar in increasing compliance. There was difficulty in administering drugs in urban areas due to gated societies, the absence of individuals during the day, and the perspective toward healthcare providers. Participants reported a lack of confidence in drug distributors and a fear of side effects as major causes for non-compliance. Conclusion: There is a need to strengthen MDA, especially in urban areas. An urban-specific strategy, along with surveillance, behavioral change communication, and the involvement of multi-disciplinary teams, is required.

Palmitate induces integrated stress response and lipoapoptosis in trophoblasts.

Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.

Effects of High-Intensity, Eccentric-Only Muscle Actions on Serum Biomarkers of Collagen Degradation and Synthesis.

ABSTRACT: Neltner, TJ, Sahoo, PK, Smith, RW, Anders, JPV, Arnett, JE, Ortega, DG, Schmidt, RJ, Johnson, GO, Natarajan, SK, and Housh, TJ. Effects of high-intensity, eccentric-only muscle actions on serum biomarkers of collagen degradation and synthesis. J Strength Cond Res 37(9): 1729-1737, 2023-The purpose of this study was to examine the effects of high-intensity, eccentric-only muscle actions of the leg extensors on (a) serum biomarkers of collagen degradation (hydroxyproline [HYP] and C-terminal telopeptide of type I collagen [C1M]) and synthesis (pro-c1α1) and (b) the time course of changes in maximal voluntary isometric contraction (MVIC) and ratings of muscle soreness after the eccentric-only exercise bout. Twenty-five recreationally active men (mean ± SD: age = 21.2 ± 2.0 years) completed 5 sets of 10 bilateral, eccentric-only dynamic constant external resistance muscle actions of the leg extensors at a load of 110% of their concentric leg extension 1 repetition maximum. Analysis of variances (p < 0.05) and a priori planned pairwise comparisons using Bonferroni corrected (p < 0.0167) paired t tests were used to examine mean changes in blood biomarkers from baseline to 48 hours postexercise as well as in MVIC and soreness ratings immediately, 24 hours, and 48 hours postexercise. There were increases in HYP (3.41 ± 2.37 to 12.37 ± 8.11 µg·ml-1; p < 0.001) and C1M (2.50 ± 1.05 to 5.64 ± 4.89 µg·L-1; p = 0.003) from preexercise to 48 hours postexercise, but no change in pro-c1α1. Maximal voluntary isometric contraction declined immediately after the exercise bout (450.44 ± 72.80 to 424.48 ± 66.67 N·m; p = 0.002) but recovered 24 hours later, whereas soreness was elevated immediately (6.56 ± 1.58; p < 0.001), 24 hours (3.52 ± 1.53; p < 0.001), and 48 hours (2.60 ± 1.32; p = 0.001) postexercise. The eccentric-only exercise bout induced increases in collagen degradation but had no effect on collagen synthesis. These findings provide information for clinicians to consider when prescribing exercise after an acute injury or surgery.

Effect of nano-metal doped calcium peroxide on biomass pretreatment and green hydrogen production from rice straw.

In this study, calcium peroxide was modified and doped with metal-based nanoparticles (NP) to enhance the efficiency of pretreatment and biohydrogen generation from RS. The findings revealed that the addition of MnO2-CaO2 NPs (at a dosage of 0.02 g/g TS of RS) had a synergistic effect on the breakdown of biomass and the production of biohydrogen. This enhancement resulted in a maximum hydrogen yield (HY) of 58 mL/g TS, accompanied by increased concentrations of acetic acid (2117 mg/L) and butyric acid (1325 mg/L). In contrast, RS that underwent pretreatment without the use of chemicals or NP exhibited a lower HY of 28 mL/g TS, along with the lowest concentrations of acetic acid (1062 mg/L) and butyric acid (697 mg/L). The outcome showed that supplementation of NP stimulated the pretreatment of RS and improved the formation of acetic and butyric acid through the regulation of metabolic pathways during acidogenic fermentation.

Unrevealing the role of metal oxide nanoparticles on biohydrogen production by Lactobacillus delbrueckii.

The positive interaction between Clostridium sp. and lactic acid-producing bacteria (Lactobacillus sp) is commonly seen in various high-rate hydrogen production systems. However, the exact role of the hydrogen production ability of Lactobacillus sp in a dark fermentation production system is rarely studied. Lactobacillus delbrueckii was herein used for the first time, to the best of the author's knowledge, to demonstrate biohydrogen production under anaerobic conditions. At first, the pH condition was optimized, followed by the addition of nanoparticles for enhanced biohydrogen production. Under optimized conditions of pH 6.5, substrate concentration 10 g/L, and 100 mg/L of NiO/Fe2O3, the maximum hydrogen yield (HY) of 1.94 mol/mol hexose was obtained, which is 18 % more than the control. The enhanced H2 production upon the addition of nanoparticles is supported via the external electron transfer (EET) mechanism, which regulates the metabolic pathway regulation with increased production of acetate and butyrate and reduced formation of lactate.

Facilitators and barriers in implementation of mass drug administration for lymphatic filariasis elimination in India: A protocol for systematic review and qualitative meta-synthesis.

Introduction: Lymphatic filariasis (LF) is a debilitating and disabling parasitic disease of immense public health concern in India with more than 650 million people at risk. Mass drug administration (MDA) is the recommended preventive chemotherapy strategy to eliminate LF. But, its coverage and compliance has been a mixed success. There is an urgent need of evidence to strengthen the program further, which can be done by exploring and understanding implementer as well as beneficiary perspectives. Objective: To systematically review the facilitators and barriers experienced during the coverage and compliance of MDA for LF elimination in India from both beneficiary and provider's (health system) perspective. Methods and Analysis: We will search at Medline database through PubMed and Embase, along with ProQuest and Google Scholar to retrieve literature. Original qualitative observational studies exploring challenges and enablers in MDA program will be screened by two independent reviewers systematically based on title and abstract followed by full text. The risk of bias will be assessed through critical appraisal skills program checklist for each included article. Data will be extracted in a pre-designed proforma with study characteristics, demographic features, and texts and quotes of qualitative data. Data will be analyzed through thematic analysis and motivation-opportunity-ability-behavior framework using MAXQDA software. Ethics and Dissemination: This is a literature-based review with minimal privacy concerns. The findings of this study will be published in a peer-reviewed journal and disseminated through policy brief to program implementers.

Transition metal-free approach for late-stage benzylic C(sp3)-H etherifications and esterifications.

We report a transition metal-free approach for the regioselective functionalization of benzylic C(sp3)-H bonds using alcohols and carboxylic acids as the nucleophiles. This straightforward and general route has provided various benzylic ethers and esters, including twelve pharmaceutically relevant compounds.

Mass drug administration for lymphatic filariasis elimination amidst COVID-19 pandemic in Odisha, India: A step towards achieving SDG-3.

Sustainable Development Goal-3 (SDG) aims to eliminate lymphatic filariasis by 2030 through >65% coverage and compliance of mass drug administration (MDA), the preventive chemotherapy strategy of delivering anthelminthic drugs. However, the ongoing COVID-19 pandemic has disrupted such programmes, yet MDA was administered during February 2021 in Odisha, India. We aimed to assess the coverage and compliance of the present round of MDA amidst the pandemic and explore factors for non-compliance in Cuttack district of Odisha, a filariasis endemic area. Community-based participants enrolled through multistage stratified sampling were administered a semi-structured questionnaire following COVID-19 protocols. The coverage of MDA was 93.2% whereas consumption was 73.7%. Participants reported that healthcare workers were motivated and satisfactorily explained the benefits of MDA but still fear of side-effects was the major cause of non-compliance. Nonetheless, this recent round of MDA was effective, despite challenges posed by the ongoing pandemic.

Expansion of the measles and rubella laboratory network, India.

Objective: To expand the measles and rubella laboratory network of India by integrating new laboratories. Methods: In collaboration with the World Health Organization (WHO), the Indian government developed a 10-step scheme to systematically expand the number of laboratories performing serological and molecular testing for measles and rubella. The Indian Council of Medical Research and WHO identified suitable laboratories based on their geographical location, willingness, preparedness, past performance and adherence to national quality control and quality assurance mechanisms. The 10-step scheme was initiated with training on measles and rubella diagnostic assays followed by testing of both measles and rubella serology and molecular unknown panels, cross-verification with reference laboratories and ended with WHO on-site accreditation. Findings: After extensive training, technical support, funding and monitoring, all six selected laboratories attained passing scores of 90.0% or more in serological and molecular proficiency testing of measles and rubella. Since 2018, the laboratories are a part of the measles and rubella network of India. Within 12 months of initiation of independent reporting, the six laboratories have tested 2287 serum samples and 701 throat or nasopharyngeal swabs or urine samples. Conclusion: The process led to strengthening and expansion of the network. This proficient laboratory network has helped India in scaling up serological and molecular testing of measles and rubella while ensuring high quality testing. The collaborative model developed by the Indian government with WHO can be implemented by other countries for expanding laboratory networks for surveillance of measles and rubella as well as other infectious diseases.

Seropositivity of Chlamydia trachomatis & Toxoplasma gondii among male partners of infertile couples in Odisha, India: A facility-based exploratory study.

Chlamydia trachomatis (CT) is the most common curable sexually transmitted non-viral infection, which can cause urethritis, prostatitis, orchitis and epididymitis among males. Toxoplasma gondii, a protozoan causes toxoplasmosis among humans. These infections may lead to decreased fertility. Hence, this study was aimed to estimate the seropositivity of CT and T. gondii infection among the male partners of infertile couples in Odisha, India. In this facility-based cross-sectional study, first void urine, seminal fluid and blood sample were collected from 153 males attending infertility clinics including 74 healthy controls. Urine and seminal fluid were tested through polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay was used to detect immunoglobulin (Ig) G, IgA and IgM anti-Chlamydia and IgM anti-Toxoplasma antibodies through serum. The prevalence of CT was 1.26 per cent (95% CI: 0.03-6.85) as estimated from semen samples using PCR. We detected anti-Chlamydia antibodies IgM-four per cent [95% confidence interval (CI): 0.83-11.24]; IgA-28.16 per cent (95% CI: 18.13-40.09) and IgG-12.5 per cent (95% CI: 5.87-22.4) among participants. Anti-Toxoplasma antibodies IgM were observed in 27.63 per cent (95% CI: 17.98-39.08) of participants. None of the control samples were found positive. Overall seropositivity of CT and Toxoplasma infections is comparable, which suggests that greater attention is required for screening these infections at clinics, especially among infertile couples.

Mapping the distribution and trends of co-circulating dengue virus serotypes in Odisha, India: A retrospective facility-based analysis.

Background Dengue, caused by mosquito bite, is an emerging disease of international concern. Evidence regarding the prevalent dengue serotypes is scarce, but essential for its management during the outbreaks. Hence, we mapped the distribution and trends of currently prevalent dengue virus (DENV) serotypes in Odisha. Methods We conducted a facility-based retrospective study from referral samples sent for the diagnosis/confirmation of dengue in 2018. The samples were serologically tested for enzyme-linked immunosorbent assay (ELISA) IgM antibody and NS1. Only NS1-positive samples were chosen for sero-typing. A pool of 8-10 NS1-positive samples were analysed for district-wise serotypes. Ribonucleic acid extraction and nested polymerase chain reaction (PCR) was done from NS1-positive samples. The PCR products were then subjected to gel electrophoresis. Results A total of 2892 samples were screened for dengue virus across various districts of Odisha where 763 samples were found to be NS1-positive. Thirteen of 18 districts covering all topographies of Odisha predominantly had DENV2 serotype. Only few districts such as Balangir, Kalahandi and Rayagada had mixed serotypes. Conclusion Although DENV2 is predominantly prevalent, mixed serotypes too exist in Odisha. Evidence based on variations of dengue serotypes across topographies, seasons, gender and age groups may support public health efforts in preventing the disease.

Viral characteristics and clinical presentation in dengue co-infection- Findings from a facility based observational study in Odisha, India.

BACKGROUND: Dengue has affected many countries globally. Two-fifths part of the world is at risk, which can be affected by dengue disease. In India, the dengue incidence has increased in the recent past and emerged as an important health problem in many states including Odisha. Dengue disease presents with atypical clinical symptoms when associated with other co-infections. MATERIALS AND METHODS: A facility-based longitudinal study was carried out over a period of 1 year to determine the dengue co-infection and its outcome. The suspected cases were clinically assessed following a standard case report format and serological investigations including serotyping were carried out. RESULTS: 33.6% samples were dengue positive of which 78.5% were positive for NS1 Ag, 26.6% positive for dengue IgM and 5.1% to both. Among the dengue positive cases, 60.9% were male and mean age was 31.52 (±17.03) years. High occurrence of cases was during May to November with maximum in August. Among the 975 dengue positives, 57 (5.8%) were found to have co-infection. Chikungunya was the most common co-infection in 71.9%, followed by herpes simplex (HSV) (7%) and other diseases. Fever was the most common presenting symptom (98.2%), followed by myalgia (91.2%), retro orbital pain (91.2%), pain abdomen (12.3%), rash/lesion (8.8%), burning micturition (5.3%), petechiae (1.7%) and pruritus (1.7%) among the co-infected cases. CONCLUSIONS: All the four dengue serotypes were found to be circulating with DEN 2 as the most predominant one. About 5.8% of dengue cases have co-infection (mainly with Chikungunya) and clinically present with atypical signs and symptoms.

Investigating immunological interaction between lymphatic filariasis and COVID-19 infection: a preliminary evidence.

The foremost concerns of COVID-19 vaccines are safety and efficacy, which becomes grave in countries with a high burden of Neglected Tropical Diseases. Studies proposed helminthic infections might alleviate the efficacy of COVID-19 vaccines. We share preliminary evidence on the association between filariasis and COVID-19 infection. We collated 2 ml of blood from 174 participants residing in filariasis endemic area. To determine filarial antigen, the Og4C3 test and for COVID-19 antibodies, tests through ELISA was performed. COVID-19 antibodies were present among 74/174 (42.5%), whereas filarial antigens were detected in 24/174 (13.8%) participants. An insignificant association [OR = 0.855 (0.36-2.034)] between two was observed. Hence, people in filarial endemic regions can continue taking vaccines without worrying about their efficacy due to the helminthic load in community.

Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis.

Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.

Burden of Rubella virus infection among females attending tertiary care hospitals of Odisha, India: a need for adult women vaccination.

Rubella is a contagious disease caused by rubella virus leading to adverse outcomes among pregnant women including abortions, low birth weight, stillbirths and congenital rubella syndrome (CRS) in the baby. If not pregnant, the clinical manifestations are mild and self-limiting. In this hospital based cross-sectional study, 1985 blood samples were collected from females attending outpatient services of various hospitals to serologically detect Rubella infection. Rubella antibodies namely Immunoglobulin M (IgM)/Immunoglobulin G (IgG) were detected through enzyme linked immunosorbent assay (ELISA) or by identifying virus through polymerase chain reaction (PCR). From the total enrolled participants, 1951 samples were tested with age ranging from 16 to 38 years. Among the positive samples, about 60% patients had IgG antibodies as compared to less than 1% IgM and 0.40% by PCR. Out of 1951 samples, 7/849 (0.82%) and 651/1070 (60.8%) had IgM & IgG rubella antibodies respectively. The odds of having abortion was [OR-13.14 (4.94-34.97)] among anti-rubella positive and primi-gravida [OR-43.6 (5.9-322)] women. Therefore, vaccination of women against rubella before planning of pregnancy or at adolescence seems to be the need of hour to avoid the ill consequences during pregnancy as well as for the new born baby.

Saturated free fatty acids induce placental trophoblast lipoapoptosis.

INTRODUCTION: Obesity during pregnancy increases the risk for maternal complications like gestational diabetes, preeclampsia, and maternal inflammation. Maternal obesity also increases the risk of childhood obesity, intrauterine growth restriction (IUGR) and diabetes to the offspring. Increased circulating free fatty acids (FFAs) in obesity due to adipose tissue lipolysis induces lipoapoptosis to hepatocytes, cholangiocytes, and pancreatic-ß-cells. During the third trimester of human pregnancy, there is an increase in maternal lipolysis and release of FFAs into the circulation. It is currently unknown if increased FFAs during gestation as a result of maternal obesity cause placental cell lipoapoptosis. Increased exposure of FFAs during maternal obesity has been shown to result in placental lipotoxicity. The objective of the present study is to determine saturated FFA-induced trophoblast lipoapoptosis and also to test the protective role of monounsaturated fatty acids against FFA-induced trophoblast lipoapoptosis using in vitro cell culture model. Here, we hypothesize that saturated FFAs induce placental trophoblast lipoapoptosis, which was prevented by monounsaturated fatty acids. METHODS: Biochemical and structural markers of apoptosis by characteristic nuclear morphological changes with DAPI staining, and caspase 3/7 activity was assessed. Cleaved PARP and cleaved caspase 3 were examined by western blot analysis. RESULTS: Treatment of trophoblast cell lines, JEG-3 and JAR cells with palmitate (PA) or stearate (SA) induces trophoblast lipoapoptosis as evidenced by a significant increase in apoptotic nuclear morphological changes and caspase 3/7 activity. We observed that saturated FFAs caused a concentration-dependent increase in placental trophoblast lipoapoptosis. We also observed that monounsaturated fatty acids like palmitoleate and oleate mitigates placental trophoblast lipoapoptosis caused due to PA exposure. CONCLUSION: We show that saturated FFAs induce trophoblast lipoapoptosis. Co-treatment of monounsaturated fatty acids like palmitoleate and oleate protects against FFA-induced trophoblast lipoapoptosis.

Association of leptospirosis and scrub typhus in acute encephalitis syndrome in a tertiary care hospital in Odisha, India.

BACKGROUND: Acute encephalitis syndrome (AES) is a major public health concern in India, causing febrile illness principally associated with viral infection. Bacteria-like scrub typhus and leptospirosis also cause acute febrile illness. Therefore, this study was conceived to address the possible etiological agents contributing to sporadic AES in a tertiary care center in Odisha, India. METHOD: This was a prospective hospital-based study that enrolled 92 consecutive patients with clinically diagnosed AES whose blood/cerebrospinal fluid samples were tested for IgM antibodies to dengue, Japanese encephalitis (JE), herpes simplex virus (HSV), Epstein-Barr virus (EBV), leptospirosis and scrub typhus. RESULTS: Viral antibodies to dengue were detected in three (3.26%) cases, HSV1 in four (4.34%) and HSV2 in three (3.26%) cases. Significantly, antibodies to EBV in 22 (23.591%) and to JE in 27 (29.34%) cases were detected. Notably, 30 (32.60%) and 11(12.0%) of patients had IgM antibodies to leptospirosis and scrub typhus, respectively. CONCLUSION: This observation indicates an association of leptospirosis and scrub typhus infection in sporadic cases of AES, besides other viruses.